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PubMed1993

Determination of iron by the Ferrochem II: interference by tuberculostatics.

Iron levels in samples from certain treated tuberculous patients are underestimated by the Ferrochem II analyser. Of the tuberculostatic drugs examined for a possible interference, isoniazid, ethambutol, rifampicin, pyrazinamide and Rifater (a mixture of rifampicin, isoniazid and pyrazinamide), only pyrazinamide and Rifater (due to its pyrazinamide content) were associated with iron levels differing significantly (p < 0.001) from those of controls, with means of -317.2 and -185.6 mumol l-1 for pyrazinamide and Rifater respectively as against 9.91 mumol l-1 for the controls. The negative interference (I) due to pyrazinamide was independent of iron level in the samples but dependent on pyrazinamide concentration in the same (P) (r = 0.9993), I = -0.4380P-0.4276.

Antitubercular Agents↗

PubMed1995

[Allopurinol hypersensitivity. A possible cause of hepatitis and mucocutaneous eruptions in a patient undergoing antitubercular treatment].

The authors describe a case of drug-induced cytolytic hepatitis probably secondary to hypersensitivity to allopurinol which was prescribed incorrectly for secondary hyperuricaemia during treatment with pyrazinamide. The diagnosis was reviewed in view of the late occurrence of hepatitis in relation to the onset of the antituberculous treatment, the absence of a viral aetiology and the presence of clinical manifestations, biological and histological features which were compatible with hypersensitivity to allopurinol. The authors recalled that the type of uricaemia induced by pyrazinamide is most often asymptomatic and does not require any treatment with uric acid lowering drugs. Cessation of pyrazinamide is justified in cases of symptomatic hyperuricaemia but when the indications for pyrazinamide are imperative, treatment with an eliminator of uric acid is indicated. Allopurinol is contra-indicated in association with pyrazinamide on account of its inhibitory reaction to xanthine oxidase. Xanthine oxidase decreases the level pyrazinoic acid, a metabolite of pyrazinamide, which is responsible for the inhibition of the tubular secretion of uric acid.

Adult↗

PubMed1987

Five-year follow-up of a controlled trial of five 6-month regimens of chemotherapy for pulmonary tuberculosis. Hong Kong Chest Service/British Medical Research Council.

In a study in Hong Kong, Chinese patients with sputum-smear-positive pulmonary tuberculosis were allocated at random to five 6-month antituberculosis regimens. Four were pyrazinamide-containing regimens: 3 of these were given 3 times a week throughout, and contained isoniazid, rifampin, and pyrazinamide together with (1) streptomycin and ethambutol (HRZSE3), (2) streptomycin but no ethambutol (HRZS3), and (3) ethambutol but no streptomycin (HRZE3). The fourth contained the same drugs as Regimen 3, but was given daily throughout (HRZE7). The fifth regimen contained isoniazid, rifampin, streptomycin, and ethambutol, given 3 times a week, but no pyrazinamide (HRSE3). As previously reported, all 833 patients with drug-susceptible strains of tubercle bacilli pretreatment had a favorable bacteriologic response during chemotherapy, and bacteriologic relapse during the 2 yr (18 months after the end of chemotherapy) occurred in 9 (1.4%) of 626 patients in the pyrazinamide series (Regimens 1 to 4 combined) compared with 13 (7.8%) of 166 in the nonpyrazinamide series (Regimen 5) (p less than 0.001). The patients have been assessed at 4 and 5 yr after admission to the study. During the 5 yr, the total relapse rates for patients with drug-susceptible strains pretreatment were 3.4% for the pyrazinamide series compared with 10.3% for the nonpyrazinamide series (p less than 0.001). The results for the pyrazinamide series were also very good for the 104 assessable patients with strains resistant to isoniazid, streptomycin, or both drugs pretreatment: there was 1 failure during chemotherapy, 1 relapse during the first 2 yr and 2 subsequent relapses.

Adolescent↗

PubMed2005

Tuberculosis in neonates and infants: epidemiology, pathogenesis, clinical manifestations, diagnosis, and management issues.

Tuberculosis is one of the leading infectious causes of death and as such represents a major global health problem. Infants may develop congenital tuberculosis from an infectious mother or, most commonly, they may acquire postnatal disease by contact with an infectious adult source. Important epidemiologic, pathogenetic, and clinical data regarding the management of infantile disease are reviewed. Diagnostic evaluation includes tuberculin skin tests, chest radiography and other imaging studies, smears and cultures, examination of the cerebrospinal fluid, and polymerase chain reaction, as well as the more recent interferon-gamma assay. Pregnant women with a positive Mantoux skin test but normal chest x-ray should either start chemoprophylaxis during gestation or after delivery depending on the likelihood of being recently infected, their risk of progression to disease, as well as their clinical evidence of disease. Pregnant women with a positive Mantoux skin test and chest x-ray or symptoms indicative of active disease should be treated with non-teratogenic agents during gestation; all household contacts should also be screened. When tuberculosis is suspected around delivery, the mother should be assessed by chest x-ray and sputum smear; separation of mother and offspring is indicated only if the mother is non-adherent to medical treatment, needs to be hospitalized, or when drug-resistant tuberculosis is involved. According to the American Academy of Pediatrics, treatment of latent infection is highly effective with isoniazid administration for 9 months. This regimen may be extended to 12 months for immunocompromised patients. When drug resistance is suspected, combination therapies, which usually consist of isoniazid with rifampin (rifampicin), are administered until the results of susceptibility tests become available. Organisms resistant to isoniazid only may be treated with rifampin alone for a total of 6-9 months. All infants with tuberculosis disease should be started on four agents (isoniazid, rifampin, pyrazinamide, and ethambutol or streptomycin) until drug susceptibility is assessed. For susceptible intrathoracic tuberculosis, isoniazid, rifampin, and pyrazinamide are administered for a total of 2 months, at which point pyrazinamide is withdrawn and the other two agents are continued for another 4-10 months depending on the severity of the disease. The same regimen may be applied in extrapulmonary tuberculosis with the exception of skeletal, miliary, and CNS disease, which require daily administration of isoniazid, rifampin, pyrazinamide, and streptomycin for 1-2 months, followed by isoniazid and rifampin daily or twice weekly for another 10 months. When drug-resistant tuberculosis is suspected, a regimen of isoniazid, rifampin, and pyrazinamide plus either streptomycin or ethambutol should be initially prescribed, until the results of susceptibility tests become available. HIV-seropositive infants with pulmonary tuberculosis should receive isoniazid, rifampin, pyrazinamide, and ethambutol or an aminoglycoside for 2 months, followed by isoniazid and rifampin for a total of at least 12 months. Apart from conventional antimycobacterial agents, novel therapeutic modalities, which stimulate the host immune system such as interleukin-2 (IL-2), IL-12, interferon-gamma, and tumor necrosis factor antagonists have been tested with promising results.

Adult↗

PubMed1981

Controlled trial of four thrice-weekly regimens and a daily regimen all given for 6 months for pulmonary tuberculosis.

Five 6-month antituberculosis regimens, allocated at random to patients with acid-fast bacilli in their sputum on microscopy, were studied. Four, given three times a week from the start, contained isoniazid and rifampicin together with (1) streptomycin, pyrazinamide, and ethambutol, (2) streptomycin and pyrazinamide, (3) streptomycin and ethambutol, or (4) pyrazinamide and ethambutol. The fifth was daily isoniazid, rifampicin, pyrazinamide, and ethambutol. All 833 patients with drug-sensitive strains of bacilli before treatment had a favourable bacteriological response during chemotherapy, and the bacteriological relapse rates during 12 months after stopping chemotherapy were 2% or less for all regimens except thrice-weekly isoniazid, rifampicin, streptomycin, and ethambutol (the only regimen without pyrazinamide), which had a relapse rate of 8%. The results were equally good for the 138 patients with bacilli resistant to isoniazid, streptomycin, or both drugs initially. The incidence of potentially serious toxicity was low. The daily regimen is relevant to programmes in which patients self-administer their drugs, and the 3 pyrazinamide-containing intermittent regimens are relevant to fully supervised outpatient programmes.

Antitubercular Agents↗

PubMed1980

Controlled clinical trial of four short-course regimens of chemotherapy for two durations in the treatment of pulmonary tuberculosis. Second report. Third East African/British Medical Research Council Study.

Four short-course chemotherapy regimens for pulmonary tuberculosis have been compared: (1) streptomycin, isoniazid, rifampicin and pyrazinamide daily for 2 months followed by daily thiacetazone plus isoniazid; (2) the same 4 drugs daily for 1 month followed by thiacetazone plus isoniazid; (3) the same 4 drugs daily for 1 month followed by twice-weekly streptomycin, isoniazid and pyrazinamide; (4) the first regimen but without pyrazinamide in the initial intensive phase. Each regimen was given for 6 and 8 months and patients were followed up to 30 months. When given for 6 months the regimen with a 2-month 4-drug intensive phase had a bacteriological relapse rate of 13% and when given for 8 months there were no relapses. When pyrazinamide was omitted in the first 2 months the relapse rates were 18% for the 6-month and 6% for the 8-month series. The regimen with the 4-drug initial phase shortened to 1 month had relapse rates of 18% and 7% respectively if the continuation phase was thiacetazone plus isoniazid. However, the relapse rates were lower, 9% and 2% respectively, when the continuation phase was twice-weekly streptomycin, isoniazid and pyrazinamide.

Adolescent↗

PubMed1966

Microbial persistence. II. Characteristics of the sterile state of tubercle bacilli.

The capability of tubercle bacilli to assume a long continued sterile state in the tissues when exposed to pyrazinamide and isoniazid is a highly specific drug-microbe phenomenon in which host participation is not critical. Although it is the pyrazinamide that possesses the sterilizing type of action, the role of the isoniazid is specific and essential. The isoniazid serves to convert a phenomenon that occurs irregularly with pyrazinamide alone into one that occurs with a high degree of uniformity. The observations suggest a competition between isoniazid and the pyrazinamide (or its parent nicotinamide) for a site or entrance in or on the tubercle bacilli and for sterilization, the isoniazid apparently must reach the site first. The rare failures to attain complete sterilization, appear to depend on the emergence of pyrazinamide-resistance which prevents the necessary dependent action of the two drugs. Populations already in the sterile state are nevertheless subject to a continued drug influence. Whether this represents a direct action on the sterile bacilli or an indirect effect produced by making the environment hostile to microbial revival, cannot be determined from the present observations.

Animals↗

PubMed1978

Controlled trial of 6-month and 8-month regimens in the treatment of pulmonary tuberculosis. First report.

Four short-course antituberculosis regimens allocated at random were studied; (1) streptomycin, isoniazid, and rifampin given daily for 6 months; (2) these 3 drugs plus pyrazinamide given daily for 2 months, followed by twice-weekly administration of streptomycin, isoniazid, and pyrazinamide; (3) a regimen that differed from regimen 2 only in that ethambutol replaced pyrazinamide, and (4) streptomycin plus isoniazid plus rifampin plus pyrazinamide given 3 times per week for 4 months, followed by streptomycin plus isoniazid plus pyrazinamide administered twice per week. The last 3 regimens were given for 6 or 8 months at random. All except 1 of 680 patients with tubercle bacilli drug-susceptible before treatment had a favorable bacteriologic response during chemotherapy. The relapse rates during the first 6 months after chemotherapy were low, except in the ethambutol series, in which 19 per cent of the patients relapsed after 6 months of treatment, and 8 per cent relapsed after 8 months. A substantial proportion of the patients with strains initially resistant to either isoniazid or streptomycin had a favorable response to their allocated regimen, but the results were not as good for those patients with strains resistant to both drugs. An important finding is that the incidences of immunologic febrile reactions to rifampin and of rifampin-dependent antibodies were very low during the 3-times-weekly regimen.

Adolescent↗

PubMed1981

Should isoniazid be used in retreatment of tuberculosis despite acquired isoniazid resistance?

The use of high-dose isoniazid in retreatment regimens for tuberculosis, despite acquired isoniazid resistance, could possibly improve therapeutic results if all or part of the organisms were resistant to only low concentrations of that drug. Furthermore, organisms resistant to low concentrations of isoniazid have been shown, on occasion, to be resistant to 2 of the retreatment drugs, ethionamide and pyrazinamide, whereas higher degrees of isoniazid resistance are associated with susceptibility to these drugs. Use of high-dose isoniazid might improve results in retreatment with ethionamide and pyrazinamide by eliminating any organisms with low degrees of isoniazid resistance that have associated ethionamide and pyrazinamide resistance. Two clinical trials concerning this topic have been reported. A controlled retreatment trial with various combinations of ethionamide, cycloserine, and pyrazinamide with and without conventional "low" doses of isoniazid (300 mg per day) showed no benefit when isoniazid was added. However, a noncontrolled trial using ethionamide and pyrazinamide with and without high doses of isoniazid, 1 to 1.5 g per day, showed marked benefit with the added isoniazid. In view of these conflicting data, the use of high-dose isoniazid in retreatment regimens needs further study, which could probably be carried out in the developing countries.

Dose-Response Relationship, Drug↗

PubMed1986

Short-course drug therapy for tuberculosis.

The cost, patient compliance considerations, and toxicity of short-course chemotherapy (SCC) and conventional 18- to 24-month treatment regimens for pulmonary tuberculosis are compared; studies of the efficacy of SCC regimens are evaluated; and the future of SCC in the United States is examined. SCC is defined as treatment for nine months or less. A definite advantage of SCC over conventional therapy in terms of cost, patient compliance, or adverse effects has not been established. A series of studies conducted by the East African-British Medical Research Council documented the efficacy of various six-month, multiple-drug regimens that contain rifampin and verified the sterilizing activity of pyrazinamide during the first two months of therapy. The studies of the Hong Kong Chest Service and British Medical Research Council documented the efficacy of several intermittent drug regimens. Acceptable relapse rates were achieved with streptomycin, isoniazid, and pyrazinamide given two or three times a week for four or six months, preceded by a two-month, multiple-drug, daily regimen, and various four-drug, pyrazinamide-containing intermittent regimens. The benefit of pyrazinamide in reducing the relapse rate with SCC was confirmed by studies of the British Thoracic and Tuberculosis Association. Few studies of SCC have been conducted in the United States. Treatment practices in the United States are becoming more uniform, and SCC is being used more frequently for uncomplicated pulmonary tuberculosis. SCC will probably be used more widely in the future. Current guidelines of the Centers for Disease Control recommend treatment for nine months with isoniazid and rifampin, plus ethambutol in areas where resistance to isoniazid is common. In vitro data suggest that the addition of pyrazinamide may be more effective, but clinical experience with this drug in the United States is limited.

Antitubercular Agents↗

PubMed1998

Subchronic toxicity of human immunodeficiency virus and tuberculosis combination therapies in B6C3F1 mice.

Combination therapy with anti-HIV drugs and opportunistic infection drugs is a common practice in treatment of AIDS patients. Although toxic effects of most individual therapies are known, the toxic potential of most combination therapies has not been established. To understand the toxic consequences of combination therapies, the commonly used anti-HIV drug 3'-azido-3'-deoxythymidine (AZT) and tuberculosis infection therapies pyrazinamide, isoniazid, and rifampicin were evaluated by 13-week gavage studies in B6C3F1 mice, either alone or AZT in combination with one of the antituberculosis drugs. The doses include AZT 100, 200, and 400; pyrazinamide 1000 and 1500; isoniazid 50, 100, and 150; and rifampicin 100, 200, and 400 mg/kg/day. AZT alone caused hematopoietic toxicity with dose-related bone marrow suppression, macrocytic anemia, and thrombocytosis. Pyrazinamide or isoniazid alone at the doses tested did not cause significant toxicity. Rifampicin alone caused hematopoietic toxicity and possibly mild hepatic toxicity. Pyrazinamide below 10 times the therapeutic dose when given with AZT did not increase the hematological toxicity of AZT. Isoniazid markedly increased the hematological toxicity of AZT and contributed to mortality at 3 to 4 times the therapeutic dose combinations. Administration of rifampicin with AZT at the calculated therapeutic doses resulted in toxicity of far greater magnitude than that caused by AZT or rifampicin alone. Combination treatment with AZT and rifampicin caused severe anemia with mortality at 2 to 4 times the therapeutic dose combinations. However, AZT did not enhance the hepatotoxicity of rifampicin. Increased hematopoietic toxicity of AZT when given in combination with the above antituberculosis drugs may be due to changes in the metabolism of AZT. Results of these studies indicate that toxicological effects of combination therapies could be considerably more severe than and different from the toxicity of individual therapies.

Animals↗

PubMed1975

Reappraisal of the activity of morphazinamide against M. tuberculosis.

Morphazinamide was shown to have an in vitro activity similar to an equimolar concentration of pyrazinamide. This activity was not due, as had been previously assumed, to pyrazinamide formed by hydrolysis from morphazinamide, since it was demonstrated in slide cultures containing tubercle bacilli which were incubated with freshly prepared dilutions of morphazinamide in acid medium for several successive periods of only 1 hour, during which time little hydrolysis occurred. A new method was used for measuring morphazinamide and pyrazinamide separately in plasma. In man, the estimated in vitro antibacterial activity was similar after approximately equimolar oral doses of morphazinamide or pyrazinamide. However, it is uncertain whether the in vivo activity of morphazinamide is the same as its in vitro activity.

Animals↗

PubMed1986

Controlled clinical trial of 4 short-course regimens of chemotherapy (three 6-month and one 8-month) for pulmonary tuberculosis: final report. East and Central African/British Medical Research Council Fifth Collaborative Study.

The bacteriological relapse rates up to 30 months after the start of chemotherapy have been compared for 4 daily short-course regimens for pulmonary tuberculosis. All 4 had the same initial 2-month intensive phase of streptomycin, isoniazid, rifampicin and pyrazinamide (SHRZ) followed by isoniazid plus rifampicin for 4 months (4HR), or isoniazid plus pyrazinamide for 4 months (4HZ), or isoniazid alone for 4 months (4H), or isoniazid alone for 6 months (6H). In patients with fully sensitive strains pretreatment, the 6-month regimen with rifampicin throughout (4HR) was highly effective, only 2% of 166 patients relapsing bacteriologically in 24 months of follow-up after stopping chemotherapy. This regimen was significantly better than the 4H regimen which had a relapse rate of 10% in 156 patients (P less than 0.02) and the 4HZ regimen which had a relapse rate of 8% in 164 patients (P = 0.05). The 6H regimen was also highly effective, only 3% of the 123 patients relapsing, compared with 10% of the 156 on the 4H regimen (P = 0.06). The relapse rate of the regimen with pyrazinamide throughout (4HZ), was not significantly different from that of either of the regimens with isoniazid alone in the continuation phase. All except 3 (1 4HR, 1 4HZ, 1 4H) of the 36 relapses were with fully drug-sensitive strains. In patients with strains resistant to isoniazid alone pretreatment none of the 23 on the 4HR or 4HZ regimens had an unfavourable bacteriological status at the end of chemotherapy compared with 8 of the 17 patients (P less than 0.005) on 4H or 6H regimens. Of the patients assessed, 3 of 20 receiving rifampicin or pyrazinamide throughout relapsed compared with 2 of 8 who did not.

Adolescent↗

PubMed1991

The management of pulmonary tuberculosis in adults notified in England and Wales in 1988. The British Thoracic Society Research Committee and the Medical Research Council Cardiothoracic Epidemiology Group.

A survey was conducted of the management of adult patients with pulmonary tuberculosis notified in England and Wales in the first 6 months of 1988. Its main aim was to record the current usage of anti-tuberculosis drugs. Information was obtained on 1026 patients (91% of those surveyed), of whom 97% were prescribed rifampicin and isoniazid as principal components of their chemotherapy. Pyrazinamide was prescribed to 80%, which represents a substantial increase on the 19% recorded in a similar survey of patients notified in 1983. Adverse reactions requiring modification of therapy occurred in 15.4% of the 332 patients starting treatment with rifampicin (R), isoniazid (H), pyrazinamide (Z) and ethambutol (E), and although the percentages were slightly lower in those who started treatment with the other main combinations of drugs, namely HRZ (14.1% of 355 patients) and HRE (12.8% of 125 patients), the differences were clinically unimportant and did not reach statistical significance. Of the patients who were prescribed pyrazinamide, only 29% received therapy approximating to the schedule now recommended as standard in the U.K., namely 2 months of triple or quadruple therapy including pyrazinamide, followed by rifampicin and isoniazid for 4 months more. This low percentage reflects the wide variation in treatment schedules and the fact that many patients continued on therapy for 9 months or more. The findings of this survey highlight the non-uniformity of prescribing practices and some of the difficulties of ensuring that patients with pulmonary tuberculosis complete an appropriate course of therapy.

Antitubercular Agents↗

PubMed1992

Antimycobacterial activity of a series of pyrazinoic acid esters.

A series of pyrazinoic acid esters has been prepared and evaluated for in vitro antimycobacterial activity. Several of the pyrazinoate esters have substantially better activity than the first-line antituberculous agent pyrazinamide against susceptible isolates of Mycobacterium turberculosis as well as activity against pyrazinamide-resistant isolates. The minimal inhibitory concentrations (MICs) were lower for each organism and at each pH than the MICs for pyrazinamide. The esters have activity against Mycobacterium bovis and Mycobacterium kansasii, two species resistant to pyrazinamide, but not against Mycobacterium avium complex.

Animals↗

PubMed1991

Effect of steroids on cerebrospinal fluid penetration of antituberculous drugs in tuberculous meningitis.

Sixteen patients with oral isoniazid, pyrazinamide, rifampin, and intramuscular streptomycin for tuberculous meningitis were studied. The concentrations of isoniazid, pyrazinamide, rifampin, and streptomycin in cerebrospinal fluid (CSF) obtained 3 hours after administration were 2.40, 34.78, 0.29, and 3.78 micrograms/ml, respectively. The CSF concentrations of isoniazid and pyrazinamide were well above the minimum inhibitory concentration for Mycobacterium tuberculosis. Concentrations of rifampin and streptomycin were above the minimal inhibitory concentration initially but declined below the minimal inhibitory concentration at later times. The CSF penetration of isoniazid, pyrazinamide, rifampin, and streptomycin was about 89%, 91%, 5%, and 20%, respectively. In eight patients who received antituberculous drugs in combination with steroids, the mean CSF and serum concentrations, as well as CSF/serum ratios at various intervals of treatment, were not statistically different (p greater than 0.05) from those of the eight patients who did not receive steroids.

Adult↗

PubMed1977

Effect of pharmacological inhibitors on urate transport during induced uricosuria.

1. The effect on urate excretion of administration of probenecid and pyrazinamide was observed in normal subjects under control conditions and after induction of uricosuria by exogenous urate loading by ribonucleic acid feeding in seven subjects, by volume loading with hypertonic sodium chloride solution infusion in 11 subjects and by partial inhibition of net urate reabsorption with uricosuric drugs in 20 subjects. 2. After ribonucleic acid feeding, the uricosuric response to probenecid was intact and ribonucleic acid feeding did not produce uricosuria after pyrazinamide. 3. After volume loading, the uricosuric response to probenecid was again intact, but infusion of sodium chloride solution still produced uricosuria after pyrazinamide administration. 4. After uricosuric drugs, the uricosuric response to probenecid was diminished. 5. These responses to probenecid and pyrazinamide may reflect different mechanisms of uricosuria. Response to pharmacological inhibitors of urate reabsorption or urate secretion may be useful for classification of induced and clinical uricosuric states.

Adult↗

PubMed1991

Treatment of tuberculosis in patients with advanced human immunodeficiency virus infection.

BACKGROUND AND METHODS: Infection with the human immunodeficiency virus (HIV) increases the risk of tuberculosis and may interfere with the effectiveness of antituberculosis chemotherapy. To examine the outcomes in patients with both diagnoses, we conducted a retrospective study of all 132 patients listed in both the acquired immunodeficiency syndrome (AIDS) and tuberculosis case registries in San Francisco from 1981 through 1988. RESULTS: At the time of the diagnosis of tuberculosis, 78 patients (59 percent) did not yet have a diagnosis of AIDS, 18 patients (14 percent) were given a concomitant diagnosis of AIDS (as determined by the presence of an AIDS-defining disease other than tuberculosis), and the remaining 36 patients (27 percent) already had AIDS. The manifestations of tuberculosis were entirely pulmonary in 50 patients (38 percent), entirely extrapulmonary in 40 patients (30 percent), and both pulmonary and extrapulmonary in 42 patients (32 percent). The treatment regimens were as follows: isoniazid and rifampin supplemented by ethambutol for the first two months, 52 patients; isoniazid and rifampin supplemented by pyrazinamide and ethambutol for the first two months, 39 patients; isoniazid and rifampin, 13 patients; isoniazid and rifampin supplemented by pyrazinamide for the first two months, 4 patients; and other drug regimens, 17 patients. The intended duration of treatment for patients whose regimen included pyrazinamide was six months, and for patients who did not receive pyrazinamide, nine months. Seven patients received no treatment because tuberculosis was first diagnosed after death. Sputum samples became clear of acid-fast organisms after a median of 10 weeks of therapy. Abnormalities on all chest radiographs taken after three months of treatment were stable or improved except for those of patients who had new nontuberculous infections. The only treatment failure occurred in a man infected with multiple drug-resistant organisms who did not comply with therapy. Adverse drug reactions occurred in 23 patients (18 percent). For all 125 treated patients, median survival was 16 months from the diagnosis of tuberculosis. Tuberculosis was a major contributor to death in 5 of the 7 untreated patients and 8 of the 125 treated patients. Three of 58 patients who completed therapy had a relapse (5 percent); compliance was poor in all 3. CONCLUSIONS: Tuberculosis causes substantial mortality in patients with advanced HIV infection. In patients who comply with the regimen, conventional therapy results in rapid sterilization of sputum, radiographic improvement, and low rates of relapse.

Acquired Immunodeficiency Syndrome↗